JP5572321B2 - Orally disintegrating tablets containing coated fine particles - Google Patents
Orally disintegrating tablets containing coated fine particles Download PDFInfo
- Publication number
- JP5572321B2 JP5572321B2 JP2009049062A JP2009049062A JP5572321B2 JP 5572321 B2 JP5572321 B2 JP 5572321B2 JP 2009049062 A JP2009049062 A JP 2009049062A JP 2009049062 A JP2009049062 A JP 2009049062A JP 5572321 B2 JP5572321 B2 JP 5572321B2
- Authority
- JP
- Japan
- Prior art keywords
- orally disintegrating
- fine particles
- disintegrating tablet
- drug
- coated fine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003826 tablet Substances 0.000 claims description 22
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
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- 239000000845 maltitol Substances 0.000 description 1
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- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
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- 239000004200 microcrystalline wax Substances 0.000 description 1
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- 239000011812 mixed powder Substances 0.000 description 1
- 239000000978 natural dye Substances 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
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- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
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- 229960002920 sorbitol Drugs 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
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- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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- 229920003169 water-soluble polymer Polymers 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Description
本発明は、主剤を含有する被覆微粒子からなり、良好な口腔内崩壊性と錠剤強度を有する口腔内崩壊錠およびその製造方法に関する。 The present invention relates to an orally disintegrating tablet comprising coated fine particles containing a main agent and having good orally disintegrating properties and tablet strength, and a method for producing the orally disintegrating tablet.
近年、高齢化社会の到来や患者のコンプライアンス向上のため、水なしでも服用可能な口腔内崩壊錠の意義が重要視されるようになってきており、実際、種々の製剤が臨床応用されつつある。その大半は、薬物が胃内に直ちに放出されるように製剤設計されたものであるが、胃酸により分解される薬物の保護や、薬物の持続放出を目的として、腸溶性もしくは徐放性皮膜を施した粒子を含有する口腔内崩壊錠も開発されている。
しかしながら、徐放性もしくは腸溶性皮膜を施した粒子を含む口腔内崩壊錠は、低圧で打錠せざるを得ないことが多いが、そうすると、錠剤強度が不十分となり、輸送時や薬局など実用上の取り扱いが困難になりがちであった。
そこで、被覆微粒子を含む口腔内崩壊錠に関して、例えば以下のような技術が文献上提案されている。
In recent years, the significance of orally disintegrating tablets that can be taken without water has become important for the arrival of an aging society and the improvement of patient compliance. In fact, various preparations are being clinically applied. . Most of the drugs are designed so that the drug is released immediately into the stomach, but enteric or sustained-release coatings are used for the purpose of protecting the drug decomposed by gastric acid and the sustained release of the drug. Orally disintegrating tablets containing the applied particles have also been developed.
However, orally disintegrating tablets containing particles with sustained-release or enteric coatings often have to be tableted at low pressure, but in this case, the tablet strength becomes insufficient, and it is practically used for transportation and pharmacies. The above handling tended to be difficult.
Thus, for example, the following techniques have been proposed in the literature regarding orally disintegrating tablets containing coated fine particles.
特許文献１には、室温を超える温度に加温して打錠することにより、被覆膜の破壊を低減する方法が開示されているが、打錠機にヒーターなど特別な装置を取り付けることを要するものである。 Patent Document 1 discloses a method of reducing breakage of the coating film by heating and tableting at a temperature exceeding room temperature, but it is necessary to attach a special device such as a heater to the tableting machine. It is necessary.
特許文献２には、塩酸タムスロシンの腸溶性徐放性微粒子を含有する口腔内崩壊錠の製造方法が開示されているが、弱圧で打錠した後、加温及び加湿し、乾燥させる工程が必須であり、操作が煩雑である。 Patent Document 2 discloses a method for producing an orally disintegrating tablet containing enteric sustained-release fine particles of tamsulosin hydrochloride. However, there is a step of heating and humidifying after tableting under low pressure and drying. It is essential and the operation is complicated.
非特許文献１には、被覆微粒子の耐胃液性を担保すべく、わざわざ７層にまで渡ってコーティングした製剤が開示されている。 Non-Patent Document 1 discloses a preparation that is purposely coated over 7 layers in order to ensure the gastric juice resistance of the coated fine particles.
これらの技術を応用した製剤は既に市販されているが、いずれも錠剤の硬度が比較的低く、取り扱い上注意が必要であった。 Formulations applying these techniques are already on the market, but all of them have relatively low tablet hardness, and need attention in handling.
また、口腔内崩壊錠に良好な崩壊性と十分な強度を持たせるために種々の検討がなされているが、特に近年ではケイ酸化合物などの無機化合物を使用した以下のような技術が文献上提案されている。 In addition, various studies have been made to give the orally disintegrating tablet good disintegration and sufficient strength. In recent years, however, the following techniques using inorganic compounds such as silicic acid compounds have been published in the literature. Proposed.
特許文献３には、無機化合物と糖類を均一に分散させた懸濁液を噴霧乾燥することにより得られる医薬組成物を圧縮成型することにより、硬度を上昇させた口腔内崩壊錠が開示されているが、この技術は噴霧乾燥用の特殊な機器及び設備や技術を必要とするものである。 Patent Document 3 discloses an orally disintegrating tablet having increased hardness by compression molding a pharmaceutical composition obtained by spray drying a suspension in which an inorganic compound and a saccharide are uniformly dispersed. However, this technique requires special equipment, equipment and technology for spray drying.
特許文献４には、錠剤の担体として糖類をメタケイ酸アルミン酸塩でコーティングした組成物を使用することにより、携帯に必要な硬度を保つ方法が開示されているが、このように無機物でコーティングされた糖類は味や口当たりが悪く、また製造工程も煩雑である。 Patent Document 4 discloses a method of maintaining hardness required for carrying by using a composition in which a saccharide is coated with metasilicate aluminate as a carrier for tablets, and is thus coated with an inorganic substance. Saccharide has a bad taste and mouthfeel, and the production process is complicated.
特許文献５には、実質的に活性成分、結晶セルロース及び無機賦形剤からなる粉末を直接圧縮形成することにより、硬度を確保する口腔内速崩壊錠が開示されているが、水に不溶性の賦形剤が製剤の大半を占めることになるため、水溶性の糖類や糖アルコール等を含む口腔内崩壊錠に味や口当たりの点で勝るとは考えにくい。 Patent Document 5 discloses an intraoral rapidly disintegrating tablet that ensures hardness by directly compressing and forming a powder consisting essentially of an active ingredient, crystalline cellulose and an inorganic excipient, but is insoluble in water. Since the excipient occupies the majority of the preparation, it is unlikely that it will be superior to the orally disintegrating tablet containing water-soluble saccharides and sugar alcohols in terms of taste and mouthfeel.
特許文献６には、乳糖および粉末セルロースを含有する医薬用組成物にメタケイ酸アルミン酸マグネシウムを添加することを特徴とする錠剤の硬度増強方法が開示されているが、高速撹拌造粒機を用いて混合粉末を複数段階に渡って造粒するため、製造工程で被覆微粒子が破壊される可能性が高い。 Patent Document 6 discloses a method for enhancing the hardness of a tablet, characterized by adding magnesium aluminate metasilicate to a pharmaceutical composition containing lactose and powdered cellulose. Since the mixed powder is granulated in a plurality of stages, it is highly possible that the coated fine particles are destroyed in the manufacturing process.
したがって、実用上十分な強度を有し、製造方法が簡易である被覆微粒子含有口腔内崩壊錠は従来の技術では、知られていなかった。 Therefore, a coated fine particle-containing orally disintegrating tablet that has practically sufficient strength and a simple production method has not been known in the prior art.
本発明は、良好な錠剤強度及び口腔内崩壊性を有する、被覆微粒子含有口腔内崩壊錠を提供することを目的とする。 An object of the present invention is to provide an orally disintegrating tablet containing coated fine particles having good tablet strength and orally disintegrating property.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、驚くべきことに、主剤を含有する被覆微粒子を適当な添加剤とともに造粒して得られる組成物にメタケイ酸アルミン酸マグネシウム粉末を添加した後打錠することによって口腔内崩壊時間に影響を与えることなく良好な錠剤強度が得られることを発見し、本願発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have surprisingly found that a composition obtained by granulating coated fine particles containing the main agent together with appropriate additives into metasilicate aluminate. It was discovered that by tableting after adding magnesium powder, good tablet strength can be obtained without affecting the disintegration time in the oral cavity, and the present invention has been completed.
すなわち、本発明の特徴は以下のとおりである。
〔１〕少なくとも以下の２成分；
（ａ）薬物含有被覆微粒子
（ｂ）メタケイ酸アルミン酸マグネシウム
を含んでなる口腔内崩壊錠であって、成分（ａ）に必要であれば速崩壊性成分を添加して得られる造粒物に、粉末状態の成分（ｂ）を添加した後、打錠することにより製造される、良好な強度を有する口腔内崩壊錠。
〔２〕薬物含有被覆微粒子が腸溶性被膜及び／又は徐放性被膜を有するものである〔１〕に記載の口腔内崩壊錠。
〔３〕薬物含有被覆微粒子の薬物がタムスロシン塩酸塩である〔１〕に記載の口腔内崩壊錠。
〔４〕タムスロシン塩酸塩含有被覆微粒子とメタケイ酸アルミン酸マグネシウムを含んでなる口腔内崩壊錠であって、前記被覆微粒子と所望の速崩壊性成分からなる造粒物に、粉末状態のメタケイ酸アルミン酸マグネシウムを添加した後、打錠することにより製造される、良好な強度を有する口腔内崩壊錠。
〔５〕少なくとも以下の２成分；
（ａ）薬物含有被覆微粒子
（ｂ）メタケイ酸アルミン酸マグネシウム
を含んでなる口腔内崩壊錠の製造方法であって、成分（ａ）に必要であれば速崩壊性成分を添加して得られる造粒物に、粉末状態の成分（ｂ）を添加した後、打錠することを特徴とする、良好な強度を有する口腔内崩壊錠の製造方法。
〔６〕薬物含有被覆微粒子が腸溶性被膜及び／又は徐放性被膜を有するものである〔５〕に記載の口腔内崩壊錠の製造方法。
〔７〕薬物含有被覆微粒子の薬物がタムスロシン塩酸塩である〔５〕に記載の口腔内崩壊錠の製造方法。
〔８〕タムスロシン塩酸塩含有被覆微粒子とメタケイ酸アルミン酸マグネシウムを含んでなる口腔内崩壊錠の製造方法であって、前記被覆微粒子と所望の速崩壊性成分からなる造粒物に、粉末状態のメタケイ酸アルミン酸マグネシウムを添加した後、打錠することを特徴とした、良好な強度を有する口腔内崩壊錠の製造方法。
That is, the features of the present invention are as follows.
[1] At least the following two components;
(A) Drug-containing coated fine particles (b) An orally disintegrating tablet comprising magnesium aluminate metasilicate, and if necessary, a granulated product obtained by adding a rapidly disintegrating component to component (a) An orally disintegrating tablet having good strength, produced by tableting after adding the component (b) in powder form.
[2] The orally disintegrating tablet according to [1], wherein the drug-containing coated fine particles have an enteric coating and / or a sustained release coating.
[3] The orally disintegrating tablet according to [1], wherein the drug of the drug-containing coated fine particles is tamsulosin hydrochloride.
[4] An orally disintegrating tablet comprising tamsulosin hydrochloride-containing coated microparticles and magnesium metasilicate aluminate, wherein the granulated product comprising the coated microparticles and a desired rapidly disintegrating component is in a powdered state. An orally disintegrating tablet having good strength produced by tableting after adding magnesium acid.
[5] At least the following two components;
(A) Drug-containing coated fine particles (b) A method for producing an orally disintegrating tablet comprising magnesium aluminate metasilicate, which is obtained by adding a rapidly disintegrating component to component (a) if necessary A method for producing an orally disintegrating tablet having good strength, comprising adding a powdered component (b) to a granule and then tableting.
[6] The method for producing an orally disintegrating tablet according to [5], wherein the drug-containing coated fine particles have an enteric coating and / or a sustained-release coating.
[7] The method for producing an orally disintegrating tablet according to [5], wherein the drug of the drug-containing coated fine particles is tamsulosin hydrochloride.
[8] A method for producing an orally disintegrating tablet comprising coated fine particles containing tamsulosin hydrochloride and magnesium aluminate metasilicate, wherein the granulated product comprising the coated fine particles and a desired rapidly disintegrating component is in a powder state. A method for producing an orally disintegrating tablet having good strength, wherein tableting is performed after adding magnesium aluminate metasilicate.
本発明によれば、実用上十分な錠剤強度を有し、製造工程中や輸送時の割れや欠けの極めて少ない、優れた被覆微粒子含有口腔内崩壊錠が提供される。さらに、本発明の口腔内崩壊錠は、錠剤強度が良好であるにも関わらず口腔内崩壊性は維持されており、簡易な工程によって製造することができる。 According to the present invention, an excellent coated fine particle-containing orally disintegrating tablet is provided that has tablet strength that is practically sufficient and has very few cracks and chipping during the production process and during transportation. Furthermore, the orally disintegrating tablet of the present invention maintains its orally disintegrating property despite its good tablet strength, and can be produced by a simple process.
（口腔内崩壊錠の構成成分）
本発明で使用される「薬物含有被覆微粒子」は、例えば薬効成分および食品成分を含む。これらは、生体内半減期が短い薬物や薬効を長時間持続させる必要のある薬物、あるいは胃酸により分解されるため胃耐性の付与が必要な薬物である。被覆微粒子は、薬物含有素粒子に常套の徐放性コーティング及び／又は腸溶性コーティングを施すことにより得られる。該薬物は、好ましくは、タムスロシン塩酸塩である。
(Components of orally disintegrating tablets)
The “drug-containing coated fine particles” used in the present invention include, for example, medicinal ingredients and food ingredients. These are drugs that have a short half-life in vivo, drugs that need to maintain their efficacy for a long time, or drugs that need to be given gastric resistance because they are degraded by stomach acid. The coated fine particles can be obtained by applying conventional sustained-release coating and / or enteric coating to drug-containing elementary particles. The drug is preferably tamsulosin hydrochloride.
本発明で使用される「メタケイ酸アルミン酸マグネシウム」としては、富士化学工業の製品（商品名ノイシリン（登録商標））が好適である。嵩比容積、水分、粒子形状、４％スラリーｐＨにより異なる各種タイプのうち、ノイシリンＵＦＬ２が最も好ましい。 The “magnesium aluminate metasilicate” used in the present invention is preferably a product (trade name Neusilin (registered trademark)) of Fuji Chemical Industry. Of the various types that vary depending on the bulk specific volume, moisture, particle shape, and 4% slurry pH, Neusilin UFL2 is most preferred.
本発明において被覆微粒子は、任意の添加剤とともに常法により造粒することができる。添加剤としては特に限定されず、賦形剤、崩壊剤、結合剤などを適宜組み合わせて使用することができるが、口当たりなどを考慮すると水溶性もしくは水親和性のものを含むのが好ましい。
賦形剤としては、乳糖、マンニトール、ソルビトール、キシリトール、トレハロース、シクロデキストリン、トウモロコシデンプン、蔗糖、結晶セルロース、無水リン酸水素カルシウム、炭酸カルシウムなどを適宜組み合わせて使用することができる。特に好ましくはＤ−マンニトールである。
崩壊剤としては、例えば、結晶セルロース、クロスポビドン、カルメロース、低置換度ヒドロキシプロピルセルロース、カルメロースカルシウム、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウム、部分α化デンプン、ヒドロキシプロピルスターチなどが挙げられる。特に好ましくは低置換度ヒドロキシプロピルセルロースである。
結合剤としては、糖類や水溶性高分子が選択され得る。例えば、マルトース、トレハロース、ソルビトール、マルチトール、グルコース、キシリトール、エリスリトール、マンニトール、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、コポリビドン、ポリビニルアルコールが挙げられる。特に好ましくは、ヒドロキシプロピルセルロースである。
In the present invention, the coated fine particles can be granulated by an ordinary method together with an optional additive. The additive is not particularly limited, and an excipient, a disintegrant, a binder, and the like can be used in appropriate combination. However, considering the mouthfeel and the like, it is preferable to include a water-soluble or water-compatible one.
As the excipient, lactose, mannitol, sorbitol, xylitol, trehalose, cyclodextrin, corn starch, sucrose, crystalline cellulose, anhydrous calcium hydrogen phosphate, calcium carbonate and the like can be used in appropriate combination. Particularly preferred is D-mannitol.
Examples of the disintegrant include crystalline cellulose, crospovidone, carmellose, low-substituted hydroxypropylcellulose, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, partially pregelatinized starch, and hydroxypropyl starch. Particularly preferred is low-substituted hydroxypropylcellulose.
As the binder, saccharides or water-soluble polymers can be selected. Examples thereof include maltose, trehalose, sorbitol, maltitol, glucose, xylitol, erythritol, mannitol, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, copolyvidone, and polyvinyl alcohol. Particularly preferred is hydroxypropylcellulose.
本発明の口腔内崩壊錠は、被覆微粒子を含む造粒物の他に、医薬品や食品の製造に一般的に用いられている甘味剤、矯味剤、流動化剤、滑沢剤、香料、着色料などをさらに含有してもよい。
甘味剤の例としては、例えば、マンニトール、デンプン糖、還元麦芽糖水あめ、ソルビット、砂糖、果糖、乳糖、蜂蜜、キシリトール、エリスリトール、ソルビトール、サッカリン、甘草およびその抽出物、グリチルリチン酸、甘茶、アスパルテーム、ステビア、ソーマチン、アセスルファムＫ、クエン酸ナトリウム、スクラロースなどが挙げられる。
矯味剤としては、クエン酸、クエン酸ナトリウム、酒石酸、ＤＬ−リンゴ酸、グリシン、ＤＬ−アラニンなどが挙げられる。
流動化剤及び／又は滑沢剤としては、含水二酸化ケイ素、軽質無水ケイ酸、ケイ酸カルシウム、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸、タルク、ラウリル硫酸ナトリウム、水素添加植物油、マイクロクリスタリンワックス、ショ糖脂肪酸エステル、ポリエチレングリコールなどが挙げられる。
香料としては、ストロベリー、レモン、レモンライム、オレンジ、ｌ−メントール、ハッカ油などが挙げられる。
着色料としては、黄色三二酸化鉄、三二酸化鉄、食用タール色素、天然色素などが挙げられる。
The orally disintegrating tablet of the present invention is a granulated product containing coated fine particles, as well as a sweetener, a corrigent, a fluidizing agent, a lubricant, a fragrance, and a coloring agent that are generally used in the manufacture of pharmaceuticals and food It may further contain a material.
Examples of sweeteners include, for example, mannitol, starch sugar, reduced maltose starch syrup, sorbit, sugar, fructose, lactose, honey, xylitol, erythritol, sorbitol, saccharin, licorice and extracts thereof, glycyrrhizic acid, sweet tea, aspartame, stevia , Thaumatin, acesulfame K, sodium citrate, sucralose and the like.
Examples of the corrigent include citric acid, sodium citrate, tartaric acid, DL-malic acid, glycine, and DL-alanine.
Fluidizing agents and / or lubricants include hydrous silicon dioxide, light anhydrous silicic acid, calcium silicate, magnesium stearate, calcium stearate, stearic acid, talc, sodium lauryl sulfate, hydrogenated vegetable oil, microcrystalline wax, shoal. Examples thereof include sugar fatty acid esters and polyethylene glycol.
Examples of the fragrances include strawberry, lemon, lemon lime, orange, l-menthol and mint oil.
Examples of the colorant include yellow iron sesquioxide, iron sesquioxide, edible tar dye, and natural dye.
（口腔内崩壊錠の製造方法）
本発明の口腔内崩壊錠は被覆微粒子と所望の添加剤を用いて、添加剤との混合物を直接、もしくは必要に応じて造粒、整粒などの工程を経た後、メタケイ酸アルミン酸マグネシウム粉末を添加して常法により打錠することによって製造される。打錠機としては、医薬品の製造に使用しうるものであれば特に制限はなく、例えばロータリー式打錠機や単発打錠機などが使用される。
(Method for producing orally disintegrating tablets)
The orally disintegrating tablet of the present invention uses coated fine particles and a desired additive, and a mixture of the additive is directly or after undergoing steps such as granulation and sizing as necessary, and then magnesium aluminate metasilicate powder And then tableted by a conventional method. The tableting machine is not particularly limited as long as it can be used for the production of pharmaceuticals. For example, a rotary tableting machine or a single-shot tableting machine is used.
以下に、実施例に基づいて本発明をより詳細に説明するが、本発明はこれらの実施例によって限定されるものではない。 Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
参考例１
タムスロシン塩酸塩1重量部、結晶セルロース４９重量部を水で混練し、乾燥、分級した。これをエチルセルロース３０重量部、ヒドロキシプロピルメチルセルロース５重量部の４％エタノール溶解液で流動層コーティングした後、分級し、徐放性微粒子を得た。この微粒子をメタクリル酸コポリマーＬＤ３０重量部、アクリル酸エチル・メタクリル酸メチルコポリマー分散液１０重量部、エチルセルロース水分散液１０重量部の１５％水分散液で流動層コーティングした後、乾燥、分級し、腸溶性徐放性微粒子として１３５重量部を得た。
この腸溶性徐放性微粒子１３５重量部、Ｄ−マンニトール８８９重量部、低置換度ヒドロキシプロピルセルロース１２５重量部を、２％ヒドロキシプロピルセルロース水溶液６重量部を間欠噴霧しながら流動層造粒し、整粒した。
Reference example 1
1 part by weight of tamsulosin hydrochloride and 49 parts by weight of crystalline cellulose were kneaded with water, dried and classified. This was fluidized bed coated with a 4% ethanol solution of 30 parts by weight of ethylcellulose and 5 parts by weight of hydroxypropyl methylcellulose, and then classified to obtain sustained-release fine particles. The fine particles were fluid bed coated with a 15% aqueous dispersion of 30 parts by weight of a methacrylic acid copolymer LD, 10 parts by weight of an ethyl acrylate / methyl methacrylate copolymer dispersion, and 10 parts by weight of an ethyl cellulose aqueous dispersion, and then dried and classified. 135 parts by weight were obtained as soluble sustained-release fine particles.
The enteric sustained-release fine particles 135 parts by weight, D-mannitol 889 parts by weight, low-substituted hydroxypropylcellulose 125 parts by weight, and fluidized bed granulation while intermittently spraying 6 parts by weight of 2% hydroxypropylcellulose aqueous solution. Grained.
実施例１
参考例１で得られた造粒物にメタケイ酸アルミン酸マグネシウム粉末（ノイシリン（登録商標）ＵＦＬ２ 富士化学工業株式会社）３０重量部、ステアリン酸Ｃａ１５重量部を添加、混合し打錠用粉末を得た。
単発打錠機（型式：Ｎｏ．２Ｂ 株式会社菊水製作所）で打錠圧６８６０Ｎで打錠し、直径８．５ｍｍの錠剤を得た。
Example 1
To the granulated product obtained in Reference Example 1, 30 parts by weight of magnesium metasilicate magnesium aluminate powder (Neusilin (registered trademark) UFL2 Fuji Chemical Industry Co., Ltd.) and 15 parts by weight of Ca stearate were added and mixed to obtain a powder for tableting. It was.
Tableting was performed with a single tableting machine (model: No. 2B Kikusui Seisakusho Co., Ltd.) at a tableting pressure of 6860N to obtain a tablet having a diameter of 8.5 mm.
比較例１
メタケイ酸アルミン酸マグネシウムの代わりに、Ｄ−マンニトールを３０重量部添加した以外は実施例１と同様の操作で錠剤を得た。
Comparative Example 1
A tablet was obtained in the same manner as in Example 1 except that 30 parts by weight of D-mannitol was added instead of magnesium aluminate metasilicate.
（試験例１）
実施例１、比較例１により得られた錠剤について、口腔内崩壊時間、引っ張り強度について確認した。引っ張り強度は、シュロイニゲル硬度計（Ｄｒ．Ｓｃｈｌｅｕｉｎｉｇｅｒ Ｐｈａｒｍａｔｒｏｎ ＡＧ）により求めた破断面積荷重から、下式にて算出した。
引っ張り強度（Ｎ／ｃｍ２）＝２×破断荷重（Ｎ）／（π×錠剤直径（ｃｍ）×錠剤厚み（ｃｍ））
その結果を以下の表１に示す。
(Test Example 1)
The tablets obtained in Example 1 and Comparative Example 1 were confirmed for oral disintegration time and tensile strength. The tensile strength was calculated by the following equation from the fracture area load determined by a Schleuniger hardness tester (Dr. Schleininger Pharmatron AG).
Tensile strength (N / cm 2) = 2 × breaking load (N) / (π × tablet diameter (cm) × tablet thickness (cm))
The results are shown in Table 1 below.
以上の結果より、実施例１の錠剤は、口腔内崩壊時間を延長させることなく硬度及び引っ張り強度が上昇することが判明した。同じく打錠圧を４９００Ｎ、８８２０Ｎとした場合においても同様の結果が得られた。 From the above results, it was found that the tablet of Example 1 increased in hardness and tensile strength without extending the oral disintegration time. Similarly, similar results were obtained when the tableting pressure was 4900N and 8820N.
（試験例２）
実施例１、比較例１と同様の操作で得た錠剤について、摩損度（％）を確認した。その結果を以下の表２に示す。摩損度の測定は第十五改正日本薬局方の錠剤の摩損度試験法に基づいたが、より過酷な状況を想定し、ドラム回転数の条件を１２５、２５０、５００回転で比較した。
(Test Example 2)
The degree of friability (%) was confirmed for the tablets obtained in the same manner as in Example 1 and Comparative Example 1. The results are shown in Table 2 below. The measurement of friability was based on the 15th revised Japanese Pharmacopoeia tablet friability test method, but the conditions of drum rotation speed were compared at 125, 250, and 500 rotations assuming a more severe situation.
以上の結果より、実施例１の錠剤は、メタケイ酸アルミン酸マグネシウム粉末の添加により摩損度についても著しく改善されることが判明した。 From the above results, it was found that the tablet of Example 1 was remarkably improved in terms of friability by adding magnesium aluminate metasilicate powder.
本発明によれば、実用上十分な錠剤強度を有し、製造工程中や輸送時の割れや欠けの極めて少ない、優れた被覆微粒子含有口腔内崩壊錠が提供される。さらに、本発明の口腔内崩壊錠は、錠剤強度が良好であるにも関わらず口腔内崩壊性は維持されており、簡易な工程によって製造することができる。 According to the present invention, an excellent coated fine particle-containing orally disintegrating tablet is provided that has tablet strength that is practically sufficient and has very few cracks and chipping during the production process and during transportation. Furthermore, the orally disintegrating tablet of the present invention maintains its orally disintegrating property despite its good tablet strength, and can be produced by a simple process.
Claims (8)
（ａ）薬物含有被覆微粒子
（ｂ）メタケイ酸アルミン酸マグネシウム
を含んでなる口腔内崩壊錠であって、成分（ａ）にＤ−マンニトール、低置換度ヒドロキシプロピルセルロースからなる速崩壊性成分を添加して得られる造粒物に、１３５重量部の（ａ）に対し３０重量部の粉末状態の成分（ｂ）を添加、混合した後、打錠することにより製造される、良好な強度を有する口腔内崩壊錠。 At least the following two components;
(A) Drug-containing coated fine particles (b) An orally disintegrating tablet comprising magnesium aluminate metasilicate, wherein a rapidly disintegrating component comprising D-mannitol and low-substituted hydroxypropylcellulose is added to component (a) It is produced by adding 30 parts by weight of the powdered component (b) to 135 parts by weight of (a) , mixing, and then tableting, and thus having good strength. Orally disintegrating tablets.
（ａ）薬物含有被覆微粒子
（ｂ）メタケイ酸アルミン酸マグネシウム
を含んでなる口腔内崩壊錠の製造方法であって、成分（ａ）にＤ−マンニトール、低置換度ヒドロキシプロピルセルロースからなる速崩壊性成分を添加して得られる造粒物に、１３５重量部の（ａ）に対し３０重量部の粉末状態の成分（ｂ）を添加、混合した後、打錠することを特徴とする、良好な強度を有する口腔内崩壊錠の製造方法。 At least the following two components;
(A) Drug-containing coated fine particles (b) A method for producing an orally disintegrating tablet comprising magnesium aluminate metasilicate, wherein the component (a) comprises D-mannitol and low-substituted hydroxypropylcellulose . The granulated product obtained by adding the components is characterized by adding 30 parts by weight of the powdery component (b) to 135 parts by weight of (a) , mixing, and then tableting. A method for producing an orally disintegrating tablet having strength.
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| CN108066304A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Tamsulosin Orally disintegrating tablet compositions with sustained release performance |
| CN108066305A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Improve the method for oral disintegrating tablet hardness and disintegration and positioning release oral disnitegration tablet |
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| JP6262490B2 (en) * | 2013-10-18 | 2018-01-17 | テイカ製薬株式会社 | Intraoral rapidly disintegrating tablet composition |
| WO2017204142A1 (en) * | 2016-05-23 | 2017-11-30 | 沢井製薬株式会社 | Intraorally disintegrable tablet containing olmesartan medoxomil |
| JP6438547B2 (en) * | 2017-08-22 | 2018-12-12 | テイカ製薬株式会社 | Intraoral rapidly disintegrating tablet composition |
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| JP2000086537A (en) * | 1998-09-11 | 2000-03-28 | Fuji Chem Ind Co Ltd | Inorganic compound saccharide composition, vehicle, rapidly disintegrating compression molded product, and their production |
| JP2002308760A (en) * | 2001-04-06 | 2002-10-23 | Taiyo Yakuhin Kogyo Kk | Composition for compression molding and use thereof |
| KR100530546B1 (en) * | 2001-07-27 | 2005-11-23 | 아스텔라스세이야쿠 가부시키가이샤 | Composition Comprising Sustained-Release Fine Particles for Quick-Disintegrating Tablets in the Buccal Cavity and Manufacturing Method Thereof |
| JP3841804B2 (en) * | 2003-10-15 | 2006-11-08 | 富士化学工業株式会社 | Composition for intraorally rapidly disintegrating tablets |
| JP4944467B2 (en) * | 2005-03-24 | 2012-05-30 | 第一三共株式会社 | Pharmaceutical composition |
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| CN108066304A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Tamsulosin Orally disintegrating tablet compositions with sustained release performance |
| CN108066305A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Improve the method for oral disintegrating tablet hardness and disintegration and positioning release oral disnitegration tablet |
| CN108066304B (en) * | 2016-11-16 | 2022-09-16 | 深圳万和制药有限公司 | Tamsulosin orally disintegrating tablet composition with sustained release performance |
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